Urokinase isolated from kidney tissue culture fluids is a glycoprotein and is one of the most promising fibrinolytic agents in the treatment of thromboembolic diseases. However, urokinase has a relatively short half-life of about 4 minutes when injected into experimental animals and about 8-30 minutes in man. This very short half-life has necessiated the usage of dosage schedule which requires large amounts of urokinase to be infused for a long period of time, in the range of 6-24 hours. Because of this, a structurally modified urokinase possessing a longer biological half-life would be very desirable.
Urokinase from human fetal kidney tissue culture has been purified to homogeneity and has a molecular weight of 32,000 and a specific activity of 250,000 units/mg. This material is a glycoprotein which contains 8% of carbohydrate with little or no sialic acid i.e., urokinase is an asialo-glycoprotein. Sialic acid is usually located at the terminals on the carbohydrate moiety of glycoproteins. It has been reported that sialylated glycoproteins display long plasma survival time following intravenous injection. On the other hand, asialo-glycoproteins with galactose or other non-reducing sugars exposed at the terminal are rapidly cleared from plasma by adsorptive pinocytosis via a liver hepatocyte recognition system as elucidated by Ashwell and colleagues (Ashwell, G., Morell, A., Adv. Enzymol. 41 99-128, 1974).